Background <p>Lateral locking plate fixation serves as an alternative to intramedullary nailing for femoral shaft fractures in patients with narrow medullary canals or existing implants. However, the optimal screw configuration—particularly working length and screw positioning—remains uncertain, especially in comminuted fractures where construct stiffness and interfragmentary strain are critical for healing.</p> Methods <p>Finite element femur models were developed based on Sawbones model. A total of 27 models were constructed by combining three bone quality conditions (high, medium, and low) with nine clinically relevant screw configurations. The effects of working length and screw positioning on interfragmentary strain and plate stress were evaluated under an 800&#xa0;N axial load simulating single-leg stance.</p> Results <p>Longer working lengths resulted in increased interfragmentary strain and plate stress. Configurations with the second screw positioned farther from the fracture site also showed elevated stress and strain. Among all models, configuration 8S_C4 (intermediate working length) demonstrated the most favorable biomechanical profile, achieving strain levels near the 5% threshold for secondary healing while maintaining relatively low plate stress. These findings were consistent across all bone quality conditions.</p> Conclusion <p>This study provides biomechanical evidence that both working length and screw positioning significantly influence construct behavior in lateral locking plate fixation of comminuted femoral shaft fractures. The 8S_C4 configuration is recommended for its optimal balance of promoting favorable strain for healing and minimizing plate stress. These insights may inform screw placement strategies to improve clinical outcomes.</p> Trial registration <p>Not applicable, this is a finite element study.</p>